Diseases of the central nervous system remain among the most compelling maladies known to humankind. This is because depression are typically devastating to affected patients and their families, often robbing individuals of the qualities that we most strongly associate with being human, and because the vast majority of neurological and neurodegenerative disorders lack effective therapies. In the 1980s and 1990s, the advent of molecular genetics approaches to map and identify disease genes laid the foundation for a prodigious advance in our understanding of the pathogenic basis of numerous important depression.
Major depressive disorder (MDD) is a chronic, disabling illness that affects a substantial proportion of the population. Despite a number of available antidepressants, response and remission rates in patients with MDD remain low, relapse is common, and many patients face a chronic struggle with the burden of depressive illness. Even in the Sequenced Treatment Alternatives to Relieve Depression study, in which patient adherence and clinical status were closely followed in a real-world setting, approximately 53% of patients did not respond to an adequate trial of a first-line selective serotonin reuptake inhibitor and only 28% reached remission. The less-than-adequate rates of successful treatment in patients with MDD can be attributed to multiple factors, including the tolerability of the antidepressant treatment, particularly if the medications have a high risk for drug-drug interactions (DDIs).
The potential involvement of free radical or oxidative damage in the pathogenesis of human disease has received an enormous amount of study in the last decade. Free radicals are atoms or molecules with unpaired electrons in their outer orbits, making them highly reactive with macromolecular structures, leading to cellular injury and homeostatic disruption. Free radicals are produced as a byproduct of normal metabolism, and endogenous mechanisms exist to reduce their formation or enhance their inactivation. Disruption of the pro-oxidant and antioxidant balance in favor of the former may be a potential fundamental mechanism of human disease. A large body of evidence supports the concept that increased production of free radicals causes or accentuates neuronal injury and leads to disease, and this evidence has recently been reviewed. Therapy aimed at boosting antioxidant defenses or reducing pro-oxidant production with free radical scavengers or antioxidants may be efficacious in preventing, ameliorating, or arresting many neurologic diseases such as depression.
Managing acute pathology of often relies on the addressing underlying pathology and symptoms of the disease. There is currently a need in the art for new compositions to treatment or delay of the onset of depression and its associated complications progression.